Nonrandom chromosome abnormalities have been identified in human myelogenous leukemia, both chronic and acute. We have previously discovered four consistent translocations and one inversion in these leukemias.Now we have shown that a translocation between chromosomes 6 and 9 in acute leukemia is associatedwith an increase in marrow basophils. The breakpoints in chromosome 9 are in the same band as that in chronic myeloid leukemia, a disorder also associated with increased basophils. We are investigating whether the same DNA region is broken in both translocations. We have shown the leukemic cells from patients who were previously treated with cytotoxic agents, such as radiation and/or chemotherapy for a primary malignant disease, had a very high frequency of loss of chromosome 5 and/or 7. We believe that these abnormalities may be markers of acute leukemia induced by mutagens, because they are rare in children and they are more common in the leukemic cells of patients who worked in industries where they were exposed to mutagenic substances than in patients not so exposed. There is a remarkably close correlation between the location of oncogenes and the chromosome abnormalities, especially translocations that we have identified in human leukemia and lymphoma. We are currently investigating the molecular nature of the breakpoint in the translocation involving chromosomes 8 and 21 in acute myeloblastic leukemia; our data show that an oncogene, c-mos, located in the same band as the breakpoint, remains on chromosome 8. With the use of in situ chromosome hybridization, we have localized another oncogene, c-src, to two chromosome locations, the end of the short arm of chromosome 1 and the long arm of chromosome 20, that are frequently involved in structural rearrangements in malignant cells. The identification of the genesthat are involved and the resultant alteration in gene function will help in designing future therapy and in preventing these diseases. (K)